Ethics committees for clinical experimentation at international level with a focus on Italy
Main Article Content
Ethics Committee, Italy, Clinical trials, Observational study, risks, Food related research, ethics
Guiding legislation and associated bureaucracy for the ethical review of clinical trials observational studies and food related research play an important role in the competitiveness of a nation in the face of tough global competition to attract sponsors and investigators. This is of particular relevance in the case of multicentre trials and multidisciplinary research. Accordingly, in this report we tried to gather in-depth knowledge of the current role and practices of ethics committees nationwide in both clinical and research settings. This mini-review aims to describe the formulation and organization of ethical committees in Italy in order to provide a focus for deliberations on ethical issues in medical and scientific research in line with human rights, as set out in the European Union charter. Furthermore, we evaluated the impact of an institution’s ethical committee intervention on reducing the time required to obtain an opinion from Research Ethics Committees by guiding investigators in addressing ethical issues in their proposed studies.
2. Furlan E. Comitati Etici in sanità: storia, funzioni, questioni filosofiche. Milano: Franco Angeli, 2015.
3. National Committee for Bioethics. I comitati per l’etica nella clinica. 2017. Available at: http:// bioetica.governo.it/media/172155/p127_2017_i-comitati-etici-per-la-clinica_it.pdf.
4. UNESCO. Guide No 1: Establishing bioethics committees. 2005. Available at: http://unesdoc.unesco.org/images/0013/001393/139309e.pdf.
5. De Panfilis L, Merlo DF, Satolli R, Perin M, Ghirotto L, Costantini M. Clinical ethics consultation among Italian ethics committee: A mixed method study. PLoS ONE 2019; 14: e0226710.
6. Rice TW. The historical, ethical, and legal background of human subjects’ research. Respir Care 2008; 53: 1325–9.
7. World Medical Association. Declaration of Helsinki: ethical principles for research involving human subjects. 2008. Available at: http://www.wma.net/en/30publications/10policies/b3/index.html.
9. Council of Europe. Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine CETS. 1997. Available at: http://conventions.coe.int/Treaty/Commun/QueVoulezVous.asp?NT=164&CM=8&DF=04/02/2013&CL=ENG
10. Charter of Fundamental Rights of the European Union. Off J Eur Union 2010; C83/393.
11. European Commission. Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. Off J Eur Union 2014; 57: 1–76.
12. Gehring M, Jommy C, Tarricone R, et al. Towards a more competitive Italy in clinical research: the survey of attitudes towards trial sites in Europe (The SAT-EU Study). Epidemiol Biostat Publ Health 2015; 12: 1–9.
13. Veerus P, Lexchin J, Hemminki E. Legislative regulation and ethical governance of medical research in different European Union countries. J Med Ethics 2014; 40: 409-13.
14. Marra L, Clementi ML. Il dibattito bioetico in ambiente laico in Italia e l’esperienza dei Comitati. In: La salute in Italia: Rapporto 1998. Roma: Ediesse, 1998.
15. National Committee for Bioethics. I comitati per l’etica nella clinica. 2017. Available at: http://bioetica.governo.it/media/172155/p127_2017_i-comitati-etici-per-la-clinica_it.pdf.
16. Cattorini P. Bioethics and ethics committees in Italy. The present situation and the perspectives. NTM N.S. 1993; 1: 129–36. https://doi.org/10.1007/BF02914108.
17. Italia. Decreto legislativo 24 giugno 2003, n. 211. Attuazione della direttiva 2001/20/CE relativa all’applicazione della buona pratica clinica nell’esecuzione delle sperimentazioni cliniche di medicinali per uso clinico. Gazzetta Ufficiale della Repubblica Italiana – Serie generale n. 184, 9 agosto 2003 (Suppl. ord. n. 130).
18. Parlamento Italiano. Legge 8 novembre 2012, n. 189. Conversione in legge, con modificazioni, del decreto-legge 13 settembre 2012, n. 158, recante disposizioni urgenti per promuovere lo sviluppo del Paese mediante un più alto livello di tutela della salute. Gazzetta Ufficiale della Repubblica Italiana – Serie generale n. 263, 10 novembre 2012 (Suppl. ord. n. 201).
19. Ethics committee in Italy: http://www.eurecnet.org/information/italy.html
20. Ministerial Decree February, 8, 2013. “Parameters for the composition and functioning of Ethics committee”, GU, 2013.
21. Savonitto S, Coppola T, Braglia P, Ciccone A. [Informed consent for clinical investigation in the critically ill patient. An introduction to the regulation 536/2014/EC on clinical investigation of medicinal products for human use, repealing Directive 2001/20/EC]. G Ital Cardiol (Rome) 2016; 17: 326–34.
22. Petrini C. Some comments on the new regulations governing ethics committees in Italy. Ann Ist Super Sanita 2014; 50: 160-2.
23. Parlamento Italiano. Legge 11 gennaio 2018 n. 3. Delega al Governo in materia di sperimentazione clinica di medicinali nonché disposizioni per il riordino delle professioni sanitarie e per la dirigenza sanitaria del Ministero della salute. Gazzetta Ufficiale della Repubblica Italiana – Serie generale n. 25, 2018.
24. https:// www.moh.govt.nz/ notebook/ nbbooks.nsf/ 0/ F21C6588D45EBA67CC257A600009C6C7/ $file/ ethical-guidelines-for-observational-studies-2012.pdf
25. Perlman M. Ethical issues in ‘observational research’. Paediatr Child Health 2000; 5: 89-90.
26. Kıraç FS. Is ethics approval necessary for all trials? A clear but not certain process. Mol Imaging Radionucl Ther 2013; 22: 73-5.
27. Italian Ministerial Circular n. 6 Gazzetta Ufficiale n. 214, 12.9.2002, Italy – Ministry of Health.
28. AIFA ruling 20.3.2008, Gazzetta Ufficiale n. 76, 31.3.2008.
29. Loder E, Groves T, MacAuley D. Registration of observational studies. BMJ 2010; 340: c950.
30. ClinicalTrials.gov. FDAAA 801 Requirements. 2017. Available at: https://clinicaltrials.gov/ct2/manage-recs/fdaaa.
31. Williams RJ, Tse T, Harlan WR, Zarin DA. Registration of observational studies: is it time? CMAJ 2010; 182: 1638-42.
32. ClinicalTrials.gov. ClinicalTrials.gov protocol registration data element definitions for interventional and observational studies. 2017. Available at: https://prsinfo.clinicaltrials.gov/definitions.html.
33. The European Network of Centres for Pharmacoepidemiology and Pharma -covigilance (ENCePP). The European Union electronic Register of Post- Authorisation Studies (EU PAS Register). 2017. Available at: http://www.encepp.eu/encepp_studies/indexRegister.shtml.
34. Boccia S, Rothman KJ, Panic N, et al. Registration practices for observational studies on ClinicalTrials.gov indicated low adherence. J Clin Epidemiol 2016; 70: 176-82.
35. Kıraç FS. Is ethics approval necessary for all trials? A clear but not certain process. Mol Imaging Radionucl Ther 2013; 22: 73-5.
36. Orchard J. For debate: should observational clinical studies require ethics committee approval? J Sci Med Sport 2008; 11: 239-42.
37. Moser B, Röggla G. Should observational clinical studies require ethics committee approval? J Sci Med Sport 2008; 11: 518.
38. Claudot F, Alla F, Fresson J, Calvez T, Coudane H, Bonaïti-Pellié C. Ethics and observational studies in medical research: various rules in a common framework. Int J Epidemiol 2009; 38: 1104-8.
39. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573-7.
40. International Committee of Medical Journal Editors (ICMJE). Preparing for submission. 2016. Available at: http://www.icmje.org/recommendations/browse/manuscriptpreparation/preparing-for-submission.html#d.
41. The BMJ. Ethics approval of research. 2017. Available at: http://www.bmj.com/aboutbmj/resources-authors/formspolicies-andchecklists/ethics-approvalresearch.
42. PLOS ONE. Submission Guidelines. 2017. Available at: http://journals.plos.org/plosone/s/submission-guidelines#loc-observationaland-field-studies.
43. The Lancet. Instructions for Authors. 2017. Available at: http://www.thelancet.com/pb/assets/raw/Lancet/authors/lancet-information-forauthors.pdf.
44. Springer. Publishing ethics. 2017. Available at: https://www.springer.com/gp/authorseditors/journal-author/journal-authorhelpdesk/publishing-ethics/14214.
45. Godfray HCJ, Beddington JR, Crute IR, Haddad L, Lawrence D, Muir JF, Toulmin C. Food security: the challenge of feeding 9 billion people. Science 2010; 327: 812-8.
46. Gostin LO. Public Health Law and Ethics: A Reader. Berkeley, University of California Press, 2010.
47. Ethics and food-related research – a guidance note: European Commission FP7 Ethical Rules, 2012.
48. EU Regulation 1924/2006. Available at: http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:2006R1924:20080304:EN:PDF
49. FAO practical guide: basic concepts of food security, FAO, Rome. 2009.
50. Hartmann M. Impact assessment of the European Clinical Trials Directive: a longitudinal, prospective, observational study analysing patterns and trends in clinical drug trial applications submitted since 2001 to regulatory agencies in six EU countries. Trials 2012; 13: 53.
51. Perrone F, Marangolo M, Di Costanzo F, et al. Insurance for independent cancer trials. Ann Oncol 2004; 15: 1722–3.
52. Gehring M, Taylor RS, Mellody M, et al. Factors influencing clinical trial site selection in Europe: the survey of attitudes towards trial sites in Europe (the SAT-EU Study). BMJ Open 2013; 3: e002957.
53. Brown L. Major changes to clinical trials regulation in the EU. Appl ClinTrials 2014.
54. Kenter MJ, Cohen AF. Re-engineering the European Union clinical trials directive. Lancet 2012; 379: 1765–7.
55. Petrini C. Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use: an overview. Istituto Superiore di Sanità, 2014. Available at: http://www.scielosp.org/pdf/aiss/v50n4/04.pdf
56. Clinical research in Europe–trials and tribulations. Lancet 2012; 379: 1764.
57. Gehring M, Jommy C, Tarricone R, et al. Towards a more competitive Italy in clinical research: the survey of attitudes towards trial sites in Europe (The SAT-EU Study). Epidemiol Biostat Publ Health 2015; 12: 1–9.
58. Agenzia Italiana del Farmaco. La sperimentazione clinica dei medicinali in Italia, 12 Rapporto Nazionale. 2013. Available at: https://www.agenziafarmaco.gov.it/ricclin/sites/default/files/files_wysiwyg/files/Pubblicazioni_OsSC/13_Rapporto_OsSC_2014%20(2).pdf
59. Sexton J. State of the world’s science. Sci Am 2012; 36–40.
60. Analysis of Clinical trials listings for Germany, France, Italy, UK, Spain, NL, Belgium, Switzerland, and Austria on the NIH database. 2012. Available at: http://clinicaltrials.gov
61. Porcu L, Poli D, Torri V, et al. Impact of recent legislative bills regarding clinical research on Italian ethics committee activity. J Med Ethics 2008; 34: 747–50.
62. Hernandez R, Cooney M, Dualé C, et al. Harmonisation of ethics committes’ practice in 10 European countries. J Med Ethics 2009; 35: 696–700.
63. EFGCP Report. The Procedure for the Ethical Review of Protocols for Clinical Research Projects in Europe and Beyond. 2012. Available at: http://www.efgcp.eu/EFGCPReports.asp?L1=5&L2=1.
64. Gehring M, Taylor RS, Mellody M, et al. Factors influencing clinical trial site selection in Europe: the survey of attitudes towards trial sites in Europe (the SAT-EU Study). BMJ Open 2013; 3: e002957.
65. Analysis of Clinical trials listings for Germany, France, Italy, UK, Spain, NL, Belgium, Switzerland, and Austria on the NIH database. 2012. Available at http://clinicaltrials.gov
66. Gehring M, Jommy C, Tarricone R, et al. Towards a more competitive Italy in clinical research: the survey of attitudes towards trial sites in Europe (The SAT-EU Study). Epidemiol Biostat Publ Health 2015; 12: 1–9.
67. Jommi C, Paruzzolo S. Public administration and R&D localisation by pharmaceutical and biotech companies: a theoretical framework and the Italian case-study. Health Policy 2007; 81: 117–30.
68. De Feo G, Frontini L, Rota S, et al. Time required to start multicentre clinical trials within the Italian Medicine Agency programme of support for independent research. J Med Ethics 2015; 41: 799–803.
69. McMahon L, Cagnazzo C, Campora S, et al. The invisible hand of Clinical Research Coordinators in supporting oncology clinical research in Italy. I Supplementi di Tumori. 2014; 15: F45.
70. Cagnazzo C, Nanni O, Campora S, et al. Clinical Trials Units in Italy: the perception of the Clinical Research Coordinators. Ann Oncol 2016; 27: iv111–2.
71. Giannuzzi V, Altavilla A, Ruggieri L, Ceci A. Clinical trial application in Europe: what will change with the new regulation? Sci Eng Ethics 2016; 22: 451–66.
72. Cagnazzo C, Campora S, Ferretti E, Arizo F, Marchesi E. New European Clinical Trial Regulation: perception and expectations in Italy. Ann Oncol 2017; 28: 1648-54.
73. De Feo G, Chiabrando G, Cannovo N, Galluccio A, Tomino C. Harmonization of the practice of independent ethics committees in Italy: Project E‑submission. PLoS One 2012; 7: e48906.
74. Dixon-Woods M, Foy C, Hayden C, et al. Can an ethics officer role reduce delays in research ethics approval? A mixed-method evaluation of an improvement project. BMJ Open 2016; 6: e011973.
75. Wolf LE, Zandecki J. Conflicts of interest in research: How IRBs address their own conflicts. IRB 2007; 29: 6–12.
76. Shetty YC, Marathe PA, Billa GV, Nambiar CP. A study to assess completeness of project application forms submitted to Institutional Ethics Committees (IEC) of a tertiary care hospital. Perspect Clin Res 2012; 3: 133–8.